Region-Dependent and Stage-Specific Effects of Stress, Environmental Enrichment, and Antidepressant Treatment on Hippocampal Neurogenesis

HIPPOCAMPUS 00:00-00 (2013), ``Region-Dependent and Stage-Specific Effects of Stress, Environmental Enrichment and Antidepressant Treatment on Hippocampal Neurogenesis``

Arnaud Tanti, Willy-Paul Westphal, Virginie Girault, Bruno Brizard,

Severine Devers, Anne-Marie Leguisquet, Alexandre Surget, and Catherine Belzung

Chronic stress and depression are associated with decrease levels of hippocampal neurogenesis. On the other hand, anti-depressants as well environmental enrichment may rely in part on their pro-neurogenic effects to improve cognition and mood. The hippocampus is curve shape structure that extends in rodents both rostro-caudally and dorso-ventrally from the septal nuclei of the basal forebrain to the temporal lobe. While the septal pole seems more implicated in cognitive aspects of the hippocampal function such as learning and memory (Moser et al., 1995), the temporal pole may underlie emotional aspects of hippocampus driven functions and contribute in anxiety ?related behaviors, motivational, and regulation of the stress response (Henke, 1990; Kjelstrup et al., 2002; Herman and Mueller, 2006). All together it is possible that environmental factors and anti-depressants have different stage- specific effects along the septo-temporal axis of the hippocampus which may not be identified by neuronal markers expressed during multiple stages of development. To address this question they used two paradigms known to reliably modulate neurogenesis: an environmental enrichment and the Unpredictable Chronic Mild Stress (UCMS) regimen with concomitant treatment with Selective Serotonin Reuptake inhibitor (SSRI) Fluoxetine. Changes in cell survival and proliferation the assessed using BrDU, and Ki67 labeling. In order to quantify distinct populations of newborn neurons according to their stage of maturation they performed triple labeling for Doublecortin (DCX), Prox-1, and Calretinin (CR). In this study they show that UCMS, fluoxetine treatment, and environmental enrichment have distinct region-specific effects on neurogenesis.